In vivo mapping of infant brain microstructure with neurite orientation dispersion and density imaging

Abstract Diffusion magnetic resonance imaging (dMRI) is a non-invasive neuroimaging technique that measures the displacement of water molecules in tissue over time. Due to its sensitivity to micron-scale water movement, which is influenced by cellular structures like membranes, axons, and myelin, dMRI is a unique method for probing tissue microstructure. Among dMRI analysis approaches, neurite orientation dispersion and density imaging (NODDI) is a biophysical modeling technique that enables the characterization of cytoarchitectural and myeloarchitectural features in the brain. The early postnatal period is characterized by rapid and dynamic biological processes such as axonal growth, dendritic arborization, and synaptogenesis—changes that alter the microstructural environment in ways that are detectable by NODDI. Thus, NODDI presents a promising approach for characterizing early brain development, offering biologically specific markers of tissue organization that are responsive to these maturational events. This review presents emerging literature on NODDI applications during early infancy, demonstrating its utility in mapping normative developmental trajectories, investigating alterations in preterm populations, and linking microstructural properties to environmental influences and emerging behavioral outcomes. While current literature offers initial insights into early microstructural development patterns, NODDI applications in infancy remain limited, and existing studies are constrained by small sample sizes, limited age coverage, and lack of longitudinal data. Nonetheless, initial evidence suggests that NODDI can complement conventional diffusion metrics and may provide novel insights into early neural maturation and plasticity. Continued application and methodological refinement of NODDI in infancy may help delineate sensitive periods of brain development and improve the interpretation of emerging neurobehavioral phenotypes.